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HIV Infection of the CNS

NAMHC Concept Clearance

Presenter:

Jeymohan Joseph, PhD

Goal:

The goal of this initiative is to encourage innovative research to comprehend the mechanisms and pathways involved in Human Immunodeficiency Virus (HIV)-1 associated CNS disease in the context of viral suppression and to identify treatment strategies to alleviate CNS complications of HIV-1.  

Rationale:

Central Nervous System (CNS) disease associated with HIV continues to persist in people living with HIV despite effective antiretroviral therapy (ART). Although excellent virologic control in the periphery and brain has been achieved, CNS disease including neurologic, neurocognitive and mental health problems are observed. Considerable gaps exist in our understanding of pathogenesis of CNS disease associated with HIV. The current understanding of HIV associated CNS disease pathogenesis is largely based on clinical phenotypes that were predominantly observed prior to the ART era or from the time where patients were transitioning to using ART. The role of associated co-morbidities, long term ART treatment and chronic inflammation in HIV associated CNS disease pathogenesis have not been fully delineated. Also, viral and host genetic factors that influence disease progression and susceptibility have remained elusive. Due to the evolving nature of CNS disease outcomes associated with HIV, there also exists a need to identify modifiable therapeutic targets and to develop new strategies to alleviate CNS disease outcomes in people living with HIV.

To address the above research gaps, this initiative encourages proposals of:

  • Basic and clinical studies to comprehend the complex mechanisms and pathways that lead to neurologic, neurocognitive and mental health problems in people living with HIV;
  • Studies to comprehend the role of neuroimmune dysfunction and chronic inflammation in the setting of co-morbidities in causation of observed HIV associated mental health disease outcomes;
  • Studies to delineate key biological markers (neuroimaging, plasma & CSF) that correlate with disease symptoms, progression, and clinically relevant information regarding cognitive, emotional, neurological, and behavioral parameters observed in HIV-1 associated CNS disease;
  • Studies to adapt and utilize tailored cognitive assessments using the RDoC framework in conjunction with other biological measures such as neuroimaging and immune profiles to phenotype disease outcomes in addition to ascertaining the pathways associated with these outcomes;
  • Studies that assess the contributions of non-infectious co-morbidities to HIV-1 associated CNS disease and reciprocal interactions of HIV-1 associated CNS disease with other neurodegenerative diseases;
  • Studies to determine the mechanisms of HIV neuropathogenesis that are unique to the aging HIV-1 infected population in the context of chronic viral suppression and associated co-morbidities;
  • Research to understand the role of viral and host genetic factors in disease progression and susceptibility;
  • Studies to identify and develop therapeutic strategies for HIV-1 associated CNS disease including the development of CNS optimized ART therapies.